NCCN Risk Reclassification in Black Men with Low and Intermediate Risk Prostate Cancer After Genomic Testing.

OBJECTIVES: To assess the utility of genomic testing in risk-stratifying Black patients with low and intermediate risk prostate cancer. METHODS: We retrospectively identified 63 Black men deemed eligible for active surveillance based on National Comprehensive Cancer Network (NCCN) guidelines, who underwent OncotypeDx Genomic Prostate Score testing between April 2016 and July 2020. Nonparametric statistical testing was used to compare relevant features between patients reclassified to a higher NCCN risk after genomic testing and those who were not reclassified. RESULTS: The median age was 66 years and median pre-biopsy PSA was 7.3. Initial risk classifications were: very low risk: 7 (11.1%), low risk: 24(38.1%), favorable intermediate risk: 31(49.2%), and unfavorable intermediate risk: 1 (1.6%). Overall, NCCN risk classifications after Genomic Prostate Score testing were significantly higher than initial classifications (P=.003, Wilcoxon signed-rank). Among patients with discordant risk designations, 28(28/40, 70%) were reclassified to a higher NCCN risk after genomic testing. A pre-biopsy prostate specific antigen of greater than 10 did not have significantly higher odds of HBR (OR:2.16 [95% CI: 0.64,7.59, P=.2). Of favorable intermediate risk patients, 20(64.5%) were reclassified to a higher NCCN risk. Ultimately, 18 patients underwent definitive treatment. CONCLUSIONS: Incorporation of genomic testing in risk stratifying Black men with low and intermediate-risk prostate cancer resulted in overall higher NCCN risk classifications. Our findings suggest a role for increased utilization of genomic testing in refining risk-stratification within this patient population. These tests may better inform treatment decisions on an individualized basis.

The genome-wide rate and spectrum of EMS-induced heritable mutations in the microcrustacean Daphnia: on the prospect of forward genetics.

Forward genetic screening using the alkylating mutagen ethyl methanesulfonate (EMS) is an effective method for identifying phenotypic mutants of interest, which can be further genetically dissected to pinpoint the causal genetic mutations. An accurate estimate of the rate of EMS-induced heritable mutations is fundamental for determining the mutant sample size of a screening experiment that aims to saturate all the genes in a genome with mutations. This study examines the genome-wide EMS-induced heritable base-substitutions in three species of the freshwater microcrustacean Daphnia to help guide screening experiments. Our results show that the 10 mM EMS treatment induces base substitutions at an average rate of 1.17 × 10-6/site/generation across the three species, whereas a significantly higher average mutation rate of 1.75 × 10-6 occurs at 25 mM. The mutation spectrum of EMS-induced base substitutions at both concentration is dominated by G:C to A:T transitions. Furthermore, we find that female Daphnia exposed to EMS (F0 individuals) can asexually produce unique mutant offspring (F1) for at least 3 consecutive broods, suggestive of multiple broods as F1 mutants. Lastly, we estimate that about 750 F1s are needed for all genes in the Daphnia genome to be mutated at least once with a 95% probability. We also recommend 4-5 F2s should be collected from each F1 mutant through sibling crossing so that all induced mutations could appear in the homozygous state in the F2 population at 70-80% probability.

Racial Differences in Incident Genitourinary Cancer Cases Captured in the National Cancer Database.

Background and Objectives: The National Cancer Database (NCDB) captures nearly 70% of all new cancer diagnoses in the United States, but there exists significant variation in this capture rate based on primary tumor location and other patient demographic factors. Prostate cancer has the lowest coverage rate of all major cancers, and other genitourinary malignancies likewise fall below the average NCDB case coverage rate. We aimed to explore NCDB coverage rates for patients with genitourinary cancers as a function of race. Materials and Methods: We compared the incidence of cancer cases in the NCDB with contemporary United States Cancer Statistics data. Results: Across all malignancies, American Indian/Alaskan Natives subjects demonstrated the lowest capture rates, and Asian/Pacific Islander subjects exhibited the second-lowest capture rates. Between White and Black subjects, capture rates were significantly higher for White subjects overall and for prostate cancer and kidney cancer in White males, but significantly higher for bladder cancer in Black versus White females. No significant differences were observed in coverage rates for kidney cancer in females, bladder cancer in males, penile cancer, or testicular cancer in White versus Black patients. Conclusions: Differential access to Commission on Cancer-accredited treatment facilities for racial minorities with genitourinary cancer constitutes a unique avenue for health equity research.

Determinants of neoadjuvant chemotherapy for urothelial muscle-invasive bladder cancer: Does location matter?

INTRODUCTION: Bladder cancer care has been increasingly concentrated in high-volume metropolitan medical centres (ie, "regionalisation" of care). We aimed to assess the potential role of geographic factors, including facility region and distance to treatment centre, as determinants of neoadjuvant chemotherapy (NAC) delivery in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) using nationally representative data from the United States. METHODS: We queried the National Cancer Database to identify patients with cT2-cT4a, N0M0 urothelial MIBC who underwent radical cystectomy (RC) from 2006 to 2015. Patients who received radiation therapy, single-agent chemotherapy, adjuvant chemotherapy or systemic therapies other than multi-agent chemotherapy were excluded. Multivariate logistic regression analysis was performed to identify independent predictors of receiving NAC. RESULTS: A total of 5986 patients met the criteria for inclusion, of whom 1788 (29.9%) received NAC and 4108 received RC alone. Younger age, increased Charlson-Deyo score, increased cT stage, increased annual income, increased distance from cancer treatment centre, treatment at an Academic Research Program or Integrated Network Cancer Program and a later year of diagnosis were independently predictive of NAC receipt. Older age, Medicare insurance and treatment in the East South Central or West South Central regions were independently associated with decreased odds of NAC receipt. CONCLUSIONS: Distance to treatment centre and United States geographic region were found to affect the likelihood of NAC receipt independently of other established predictors of success in this quality-of-care metric. Access to transportation and related resources merits consideration as additional pertinent social determinants of health in bladder cancer care.

Inguinal hernia of the distal ureter causing hydronephrosis: A rare case.

Ureteral involvement in inguinal hernias is a rare occurrence. A 63-year-old man presented for surveillance of renal cell carcinoma with new onset mild intermittent flank pain. CT scan revealed new left hydroureteronephrosis to the level of the inguinal canal with dilated segments of ureter within an inguinal hernia. The patient underwent robot-assisted laparoscopic left ureterolysis and hernia repair. Ureter-containing inguinal hernias represent an uncommon but important source of obstructive uropathy. When encountered, robotic hernia repair provides a safe and effective treatment option.

Determinants of adequate lymph node dissection following neoadjuvant chemotherapy in patients with urothelial muscle-invasive bladder cancer: results from the National Cancer Database.

PURPOSE: Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymph node dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. METHODS: We queried the National Cancer Database to identify patients from 2006-2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). RESULTS: A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119-3.599], p < 0.001). The likelihood of adequate PLND was significantly decreased in patients of older age (0.607 [0.441-0.835], p = 0.002 for age 70-79 years; 0.459 [0.245-0.860], p = 0.015 for age ≥ 80 years), a Charlson-Deyo score of 1 (0.722 [0.537-0.971], p = 0.031), and those who were uninsured (0.530 [0.292-0.964], p = 0.038). CONCLUSIONS: Established predictors of PLND may not necessarily be generalizable to all patients undergoing treatment for bladder cancer. The interplay between PLND and NAC merits further study, particularly in view of recent literature calling into question the survival benefit of PLND in patients pre-treated with NAC.

Management of Vesicoureteral Reflux in a Patient With Recurrent Febrile Urinary Tract Infections, Neurogenic Bladder, and Ureteral Triplication.

Ureteral triplication is a rare anomaly with about 100 total cases reported in the literature. In this case presentation, we present a case of ureteral triplication in a young female with a history of neurogenic bladder secondary to L5 lipomeningocele who presented with recurrent febrile urinary tract infections (UTIs) and vesicoureteral reflux despite antibiotic prophylaxis. Given her high grade reflux, she underwent ureteral reimplantation which ultimately led to resolution of her UTIs and reflux. Later in her clinical course, toilet training unmasked additional bladder dysfunction and she was successfully managed with clean intermittent catheterization and anticholinergics. To the best of our knowledge, this is the first case report to describe ureteral triplication, recurrent febrile UTIs and vesicoureteral reflux in the setting of a concomitant neurogenic bladder with a successful outcome.

An audit of routine practice: a prospective study on the use of mouth props in oral surgery.

Introduction Mouth props are routinely used for patients treated under general but not local anaesthesia (LA). Patient discomfort and excess operator time is an often cited argument against the routine use of mouth props.Aim and methods We surveyed patients, surgeons and assistants following the use of mouth props during minor oral surgical procedures under LA in order to assess their acceptability and utility in clinical practice.Results Forty-seven patients were included, with 24 patients treated using mouth props and 23 without. Thirty-three patients had dental extractions, three had intraoral biopsies and one underwent a tube removal following cyst marsupialisation.Discussion Patients reported less difficulty in mouth opening where a mouth prop was used. Patients reported similarly low levels of discomfort with or without a mouth prop. Ninety-five percent of patients who used a mouth prop reported they would recommend their use. The surgeon and assistant reported mouth opening as less problematic and assisting as easier where a mouth prop was used.Conclusion The results of this study demonstrate the benefits and broad acceptability of mouth prop use in the awake patient. We question current practice in that mouth props are not routinely offered to patients during oral surgical and dental procedures.

Well-being and education of urology residents during the COVID-19 pandemic: Results of an American National Survey.

BACKGROUND: The rapid spread of COVID-19 has placed tremendous strain on the American healthcare system. Few prior studies have evaluated the well-being of or changes to training for American resident physicians during the COVID-19 pandemic. We aim to study predictors of trainee well-being and changes to clinical practice using an anonymous survey of American urology residents. METHODS: An anonymous, voluntary, 47-question survey was sent to all ACGME-accredited urology programmes in the United States. We executed a cross-sectional analysis evaluating risk factors of perception of anxiety and depression both at work and home and educational outcomes. Multiple linear regressions models were used to estimate beta coefficients and 95% confidence intervals. RESULTS: Among ~1800 urology residents in the USA, 356 (20%) responded. Among these respondents, 24 had missing data leaving a sample size of 332. Important risk factors of mental health outcomes included perception of access to PPE, local COVID-19 severity and perception of susceptible household members. Risk factors for declination of redeployment included current redeployment, having children and concerns regarding ability to reach case minimums. Risk factors for concern of achieving operative autonomy included cancellation of elective cases and higher level of training. CONCLUSIONS: Several potential actions, which could be taken by urology residency programme directors and hospital administration, may optimise urology resident well-being, morale, and education. These include advocating for adequate access to PPE, providing support at both the residency programme and institutional levels, instituting telehealth education programmes, and fostering a sense of shared responsibility of COVID-19 patients.

Heat stress incident prevalence and tennis matchplay performance at the Australian Open.

OBJECTIVES: To examine the association of wet bulb globe temperature (WBGT) with the occurrence of heat-related incidents and changes in behavioural and matchplay characteristics in men's Grand Slam tennis. DESIGN: On-court calls for trainers, doctors, cooling devices and water, post-match medical consults and matchplay characteristic data were collected from 360 Australian Open matches (first 4 rounds 2014-2016). METHODS: Data were referenced against estimated WBGT and categorised into standard zones. Generalised linear models assessed the association of WBGT zone on heat-related medical incidences and matchplay variables. RESULTS: On-court calls for doctor (47% increase per zone, p=0.001), heat-related events (41%, p=0.019), cooling devices (53%, p<0.001), and post-match heat-related consults (87%, p=0.014) increased with each rise in estimated WBGT zone. In WBGT's >32°C and >28°C, significant increases in heat-related calls (p=0.019) and calls for cooling devices (p<0.001), respectively, were evident. The number of winners (-2.5±0.006% per zone, p<0.001) and net approaches (-7.1±0.008%, p<0.001) reduced as the estimated WBGT zone increased, while return points won increased (1.75±0.46, p<0.001). When matches were adjusted for player quality of the opponent (Elo rating), the number of aces (5±0.02%, p=0.003) increased with estimated WBGT zone, whilst net approaches decreased (7.6±0.013%, p<0.001). CONCLUSIONS: Increased estimated WBGT increased total match doctor and trainer consults for heat related-incidents, post-match heat-related consults (>32°C) and cooling device callouts (>28°C). However, few matchplay characteristics were noticeably affected, with only reduced net approaches and increased aces evident in higher estimated WBGT environments.

Heat stress incidence and matchplay characteristics in Women's Grand Slam Tennis.

OBJECTIVES: To explore the relationship of wet bulb globe temperature (WBGT) on heat-related incidents and alterations in matchplay and behavioural characteristics in women's tennis at the Australian Open. DESIGN: From 360 main draw Australian Open women's matches (2014-2016), data describing on-court calls for trainers, doctors, cooling devices and water, post match medical consults and matchplay characteristics were collated. METHODS: Data were referenced against estimated WBGT and categorised into standard zones (zone 5: >32.3°C, zone 4: 30.1-32.2°C, zone 3: 27.9-30°C, zone 2: 22.3-27.9°C, zone 1: <22.2°C). Generalized linear models assessed the association of WBGT zone on heat-related medical incidences, court call-outs and match characteristics. RESULTS: With an increased estimated WBGT zone, there was an increase in total trainer calls (+19.5%/zone; p=0.019), total doctor calls (+54.1%; p<0.001), total calls for heat related incidents (+55.9%; p<0.001), and cooling devices (+31.4%; p<0.001) calculated from the regression slope. When match characteristics were adjusted for match quality, significant decreases (p<0.001) in the number of winners and net approaches and increase in double faults were associated with increased estimated WBGT zone. CONCLUSIONS: An association between higher estimated WBGT and medical callouts (heat and non-heat related) was evident, with an increased call rate >32°C WBGT, despite no heat-related retirements. As estimated WBGT increased, the number of winners and net approaches were reduced, while double faults increased, particularly >30°C WBGT. Accordingly, the manner in which female players manage and play in the heat during women's Grand Slam tennis appears to change at ≈30°C WBGT.

Penile Preservation With Subcutaneous Transposition During Fournier's Gangrene.

A 50-year-old male with past medical history of diabetes mellitus presented with extensive Fournier's Gangrene. He had a wide-spread area of involvement and the wound vacuum placement involved the entirety of the phallus. We describe a surgical technique where the penis can be diverted from the site of the wound to allow for more secure wound vacuum placement and future reconstructive options.

Induction of phenotypic plasticity in rattlesnake trophic morphology by diet manipulation.

Gape-limited predators are restricted in the shape and size of prey items they can ingest by their trophic morphology. Evolutionary theory predicts that gape-limited predators, such as rattlesnakes, should possess plasticity in their trophic morphology to allow them to respond to environmental cues about their prey base. This study examined the effects of two possible influences over trophic morphology in the pit-viper Crotalus viridis viridis. Snakes from six litters were exposed to diet manipulations performed over 480 days. By day 480, snakes from two prey-size treatments exhibited significantly different head shapes. Snakes reared on whole rodents had broader heads, whereas snakes force-fed homogenized prey had narrower heads. Shape differences varied among litters, suggesting that not all litters responded the same to diet manipulations. Results suggest that trophic morphology of rattlesnakes is plastic, at least in some litters, and can be induced by prey items.

Metabolic cost of venom replenishment by Prairie Rattlesnakes (Crotalus viridis viridis).

Snakes demonstrate a great deal of variation in the amount of venom injected in both predatory and defensive strikes. There is some evidence that snakes can adaptively meter venom dosage. An underlying assumption in the evolution of venom metering is that the production of venom is energetically costly. To date there has been very little research that has quantified the metabolic costs associated with venom production. We used open-flow respirometry to test for significant differences between Prairie Rattlesnakes (Crotalus v. viridis) that had venom extracted and control snakes that did not. Although previous studies demonstrated high metabolic costs for venom production, we found that snakes that had venom extracted did not have significantly higher metabolic rates than control snakes. The pattern of metabolic deviation from baseline measurements was similar for both treatments, and on average snakes that had venom extracted only exhibited a 1.1% increase over baseline compared to a 2.5% increase in control snakes. Our data suggest that venom is not energetically costly to produce and that perhaps other costs associated with venom can better explain the variability in venom expenditure.

Two separate synchronous primary genitourinary tumors.

A 54-year-old man presented to the office with gross painless hematuria, dysuria, and urinary frequency. He was diagnosed with renal cell carcinoma of the kidney and transitional cell carcinoma of the bladder. The article reviews the presentation, radiology, pathology, and intervention of an uncommon case of synchronous primary carcinomas, and aims to show the importance of continued clinical suspicion for multiple genitourinary primary neoplasms.